Carbamic acid, N-(3-amino-2,2-dimethyl-3-oxopropyl)-, 1,1-dimethylethyl ester synthesis

Yield:905831-26-7 71%

Reaction Conditions:

Stage #1: 3-(tert-Butoxycarbonyl)amino-2,2-dimethylpropanoic Acidwith triethylamine in tetrahydrofuran at 0; for 0.333333 h;
Stage #2: with isobutyl chloroformate in tetrahydrofuran at 0; for 1 h;
Stage #3: with ammonium hydroxide in tetrahydrofuran at 0 - 20; for 22 h;

Steps:

tertbutyl N-(2- carbamoyl-2,2-dimethylethyl)carbamate (363)

TEA (5.73 ml, 41 .08 mmol) was added to an ice-cooled (0°C) solution of 3-{[(tert-butoxy)carbonyl]amino}- 2,2-dimethylpropanoic acid (361 ) (5.25 g , 24.16 mmol) in THF (50 ml). The reaction was stirred for 20 min, before the addition of 2-methylpropyl carbonochloridate (4.7 ml, 36.3 mmol) dropwise at 0°C. The reaction was stirred for 1 h before the dropwise addition of 35% NH₃ (aqueous solution) (7.48 ml, 135.31 mmol).The reaction mixture was warmed to room temperature and stirred for22 h. Saturated NaHC0₃ (100 ml) was added and the aqueous layer extracted with DCM (3 x 150 ml). The combined organic layers were dried (MgSC), filtered and evaporated to give an off-white semi-solid (6.61 g). Purification by flash column chromatography (eluting with a gradient of 0-10% MeOH / DCM) gave the title compound (3.7 g, 71 %) as a white solid . 1 H-NMR (CDCI₃, 250 MHz): d[ppm]= 5.95 (s, 1 H), 5.30 (s, 1 H), 5.08 (s, 1 H), 3.25 (d , J = 6.6 Hz, 2H), 1 .43 (s, 9H), 1 .21 (s, 6H) HPLCMS (Method A): [m/z]: 239.10 [M+Na]⁺

References:

WO2017/68089,2017,A2 Location in patent:Page/Page column 322